Methadone for Mechanical Ventilation

(IMPACTOR Trial)

Overseen By Elizabeth Vidales

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Fentanyl, Hydromorphone

Must not be taking: Schedule II narcotics

Disqualifiers: Opioid abuse, Spinal injury, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration of hospital stay

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how methadone affects the duration critically ill patients spend on mechanical ventilators in the hospital. Researchers aim to determine if methadone can safely enable patients to breathe independently sooner, potentially shortening their hospital stay. The trial includes patients who have been on a ventilator for over 72 hours and have not passed a breathing test to assess independent breathing capability. Participants will either receive methadone or not, to compare outcomes. As a Phase 4 trial, methadone is already FDA-approved and proven effective, and this research seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have been on schedule II narcotics for more than 6 months or on other analgesic infusions besides Fentanyl or Hydromorphone.

What is the safety track record for methadone?

Research has shown that methadone is generally safe for critically ill patients who require mechanical ventilation. Studies have found that methadone effectively manages pain without causing major side effects. Most patients tolerate it well, though some may experience minor issues like nausea or constipation, which are common with many pain medications.

The FDA has already approved methadone for treating severe pain and opioid addiction. Its established safety in these areas suggests it can also be safe for patients using breathing machines. This trial aims to confirm methadone's safety for critically ill patients and to identify any side effects in this specific group. Always consult a healthcare professional before joining a trial to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for patients on mechanical ventilation, such as sedatives and opioids, primarily aim to provide comfort and sedation. However, methadone offers a unique advantage due to its long-acting properties and ability to provide stable pain relief with fewer fluctuations in sedation levels. Researchers are excited about methadone because it could potentially reduce the need for frequent dosing and adjustments, which can be particularly beneficial in managing prolonged mechanical ventilation. This stability might also contribute to smoother weaning processes from ventilation, potentially improving patient outcomes and recovery times.

What evidence suggests that methadone might be an effective treatment for reducing the duration of mechanical ventilation?

This trial will compare methadone with a non-methadone approach for patients on mechanical ventilation. Research suggests that methadone, administered to participants in the methadone group, might help patients on breathing machines recover more quickly. Some studies have found that methadone can shorten the time patients need mechanical ventilation, allowing them to breathe independently sooner. Methadone may help by reducing the need for other pain medications, which can complicate weaning from the machine. However, the quality of these studies varies, and more research is needed to confirm these results. Methadone is already known to be effective for pain relief and treating opioid addiction, supporting its potential use in this context. ^{1 3 5 6 7}

Who Is on the Research Team?

Pascal Kingah, MD, MPH

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for critically ill patients who've been on mechanical ventilation and opioid pain meds like Fentanyl or Hydromorphone for over 72 hours, are stable, and have had unsuccessful breathing trials. It's not for those with a history of opioid abuse, chronic narcotic use, certain heart or liver conditions, neuromuscular diseases, or without feeding tubes.

Inclusion Criteria

I have been on a breathing machine for more than 3 days.

My heart and blood pressure are stable.

I have been given Fentanyl or Hydromorphone for over 72 hours.

Exclusion Criteria

Patients with QTc increase of ≥60 milliseconds above the value of prior EKGs measured during current ICU admission

I have been on strong painkillers for more than 6 months before being admitted to the ICU.

I have severe liver disease and am not on warfarin with high INR and bilirubin levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive methadone or standard care while on mechanical ventilation

Duration of hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview The study tests if methadone can reduce the time critically ill patients need mechanical ventilation. Participants will either receive usual care or be given methadone. The main focus is to compare ventilator-free days from enrollment to discharge and assess safety and hospital stay length.

How Is the Trial Designed?

Group I: Methadone group Experimental Treatment 1 Intervention

Group II: Non-Methadone group Active Control 1 Intervention

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

Methadone is a unique opioid that not only acts on mu receptors but also has effects on delta receptors and NMDA receptors, making it a complex option for pain management, especially in cases of uncontrolled pain or when other opioids cause toxicity.

While methadone can be safer at lower doses, there are significant risks associated with high doses, including prolonged QT interval and potential for serious heart issues, highlighting the need for more research through randomized controlled trials to better understand its safety and efficacy compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. Bryson, J., Tamber, A., Seccareccia, D., et al.[2019]

A study of 39 patients undergoing opioid rotation from methadone to alternative opioids found that the mean dose ratio for oral methadone to oral morphine equivalent daily dose was 1:4.7, and for intravenous methadone, it was 1:13.5, indicating significant differences in potency between the two forms.

The research suggests that these new dose ratios can help clinicians switch patients to alternative opioids more safely, especially when managing side effects or inadequate pain control from methadone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Walker, PW., Palla, S., Pei, BL., et al.[2018]

Between 2001 and 2005, there were 206 reported methadone-associated deaths in Victoria, Australia, primarily due to drug toxicity, highlighting the risks associated with methadone use, especially when combined with other CNS depressants.

A significant number of deaths (25%) occurred within 14 days of starting opioid replacement therapy with methadone, often linked to high starting doses and rapid dose increases, suggesting that better management during the induction phase could help reduce mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of methadone deaths between 2001 and 2005 in Victoria, Australia. Pilgrim, JL., McDonough, M., Drummer, OH.[2013]

In a study of 52 cancer patients, rotating to methadone for pain management was effective, achieving adequate pain relief in 89% of patients within 3 days, particularly for those with mixed nociceptive-neuropathic pain.

The study suggests that using a fixed equianalgesic ratio of 10:1 for patients with a morphine-equivalent daily dose (MEDD) under 400 mg may be sufficient, indicating a tailored approach to opioid rotation can enhance pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone rotation for cancer pain: an observational study. Tan, C., Wong, JF., Yee, CM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12266829/

Methadone for critically ill patients under mechanical ... Overall, in low-quality studies with a high risk of bias, the use of methadone was associated with improved ventilation-associated outcomes and ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/46/NCT06110546/Prot_SAP_000.pdf

Impact of Methadone on prolonged mechanical ventilation ... Our study focus is to identify patients that have been on the ventilator for more than 72 hours receiving fentanyl infusions or its ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1036731425000700

Opioid administration and weaning practices in ... The primary outcome was the association between patient and opioid infusion factors with failed weaning events, defined as a ≥10% reduction from the average ...

4. researchgate.net researchgate.net/publication/393374159_Methadone_for_critically_ill_patients_under_mechanical_ventilation_in_the_intensive_care_unit_a_systematic_review

(PDF) Methadone for critically ill patients under mechanical ... The primary outcome was the duration of mechanical ventilation. The secondary outcomes included opioid-associated adverse effects and scores ...

5. scielo.br scielo.br/j/ccsci/a/g6Xg65DdzWQVVYjCfRNQd9L/

Methadone for critically ill patients under mechanical ... The primary outcome was the duration of mechanical ventilation. The secondary outcomes included opioid-associated adverse effects and scores regarding pain, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06110546

Impact of Methadone on Prolonged Mechanical Ventilation ... Impact of Methadone on Prolonged Mechanical Ventilation in Patients on Continuous Treatment With Opioids, a Randomized Trial (IMPACTOR Study). Conditions.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40767695/

Methadone for critically ill patients under mechanical ... The primary outcome was the duration of mechanical ventilation. The secondary outcomes included opioid-associated adverse effects and scores ...